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Trial registered on ANZCTR


Registration number
ACTRN12617000594325
Ethics application status
Approved
Date submitted
19/04/2017
Date registered
27/04/2017
Date last updated
11/03/2019
Date data sharing statement initially provided
11/03/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Psychosocial Aspects of Genomic Testing for Breast Cancer Risk
Scientific title
Psychosocial aspects of genomic testing for breast cancer risk among with a high risk family history of breast cancer.
Secondary ID [1] 291704 0
RG 15-22
Universal Trial Number (UTN)
U1111-1195-4653
Trial acronym
Linked study record
The parent study, ViP, aims to investigate the role of genomic variants in women at high risk of breast cancer. As such it is not registered clinical trial.

The study ethics number is: HREC/11/PMCC/43

Reference publication: Sawyer S, Mitchell G, McKinley J, Chenevix-Trench G, Beesley J, Chen XQ, Bowtell D, Trainer AH, Harris M, Lindeman GJ, James PA. A role for common genomic variants in the assessment of familial breast cancer. J Clin Oncol. 2012 Dec 10;30(35):4330-6.

Health condition
Health condition(s) or problem(s) studied:
breast cancer 302876 0
Condition category
Condition code
Mental Health 302419 302419 0 0
Studies of normal psychology, cognitive function and behaviour

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study aims to assess the psychological and behavioural outcomes associated with receiving personal polygenic breast cancer risk results.

Intervention: uptake of polygenic breast cancer risk results.

Participants in this study will be invited by letter to take part in the study and receive their personal polygenic breast cancer risk result. The invitation packet includes: a study invitation letter, participant information and consent form, and an educational leaflet describing polygenic risk. The leaflet has been pilot tested in a previous study.

Participants have undergone genomic testing and had their individual polygenic risk score (PRS) calculated as part of the parent ViP study. Participants recruited to the ViP study have provided blood samples either through a Familial Cancer Clinic (index cases) or collected at their local pathology collection center (family members recruited through index cases). Individual PRS was calculated based on 64 common risk variants. PRS is a log-additive score, calculated by weighing each risk variant by the log of the per-allele odds ratio as measured in this cohort. For further information on this please see Sawyer, et al. 2012, J. Clin. Oncol.

Participants who opt to receive their results will attend a one-off, face to face appointment of approximately 1 hour, with a qualified genetic counsellor and/or a clinical geneticist at one of the six participating familial cancer clinics. These sites include: Peter MacCallum Cancer Centre, Royal Melbourne Hospital, Austin Health, Monash Health, Cabrini Hospital, and the Royal Hobart Hospital.

The intervention received will be personalized to the participant. This is because participants are receiving their own personal polygenic risk. Furthermore, each participant has their own unique personal and family history of breast cancer which influences their individual breast cancer risk assessment. Therefore, any discussion of breast cancer risk and risk management strategies will be personalised in accordance to the individual’s polygenic risk result, and personal/family history of breast cancer.

As polygenic information represents a new test in the familial cancer setting, genetic health professionals participating in the study have completed training on the return of this information. The training has included a one day workshop which covered education on polygenic risk, its implications for breast cancer risk prediction, and methods of communicating polygenic risk results. The workshop was developed by A/Prof. Paul James (clinical geneticists and ViP study principal investigator), Ms Mary Anne-Young (senior genetic counsellor Peter MacCallum Cancer Centre) and A/Prof. Kristine Barlow Stewart (Director, Masters of Genetic Counselling University of Sydney). Genetic health professionals also have the opportunity to observe senior clinicians (A/Prof James and Ms Young) return PRS results to study participants. A training manual and visual aids have also been developed to facilitate patient communication. Finally, a sample report has been developed based on a previous qualitative study.
Intervention code [1] 297784 0
Prevention
Intervention code [2] 297785 0
Lifestyle
Intervention code [3] 297786 0
Behaviour
Comparator / control treatment
Psychological and behavioural outcomes will be compared between participants who opt to receive their PRS results (receivers) and those who opt not to receive their results (decliners)

Psychological and behavioural outcomes will also be compared based on personal history of breast cancer (affected or unaffected) and individual PRS results (high or low), such that four groups will be compared:
1) Affected high PRS
2) Affected low PRS
3) Unaffected high PRS
4) Unaffected low PRS
Control group
Active

Outcomes
Primary outcome [1] 301776 0
M9: Breast cancer specific anxiety: will be assessed by the Impact of Events Scale
Timepoint [1] 301776 0
For participants who opt to receive their results, this will be measured at baseline (Q1), 2 weeks after receipt of results (Q2), and 12 months after receipt of results (Q3).

For participants who opt not to receive their results this will be measured at baseline (Q1), and 12 months after consenting to the study (Q3)
Secondary outcome [1] 333829 0
M2: Intention to receive results - single question to assess intention to receive their personal polygenic risk result
Timepoint [1] 333829 0
Q1 - Baseline
Secondary outcome [2] 333830 0
M3: Perceived breast cancer severity severity – will be assessed with one item adapted from Kasparian, N., et al., (2009) Genetics in Medicine, 11(4): p. 265-278.
Timepoint [2] 333830 0
Q1 - Baseline
Secondary outcome [3] 333831 0
M4: Perceived risk – will be assessed with three items adapted from Kasparian, N., et al., (2009) Genetics in Medicine, 11(4): p. 265-278.
Timepoint [3] 333831 0
For participants who opt to receive their results, this will be measured at baseline (Q1), 2 weeks after receipt of results (Q2), and 12 months after receipt of results (Q3).

For participants who opt not to receive their results this will be measured at baseline (Q1), and 12 months after consenting to the study (Q3)
Secondary outcome [4] 333832 0
M5: Response efficacy (perceived benefits of receiving results) – will be assessed using six items have been adapted from Kasparian, N., et al., (2009) Genetics in Medicine, 11(4): p. 265-278.
Timepoint [4] 333832 0
Q1 - Baseline
Secondary outcome [5] 333833 0
M6: Response cost (perceived barriers to receiving results ) – will be assessed using six adapted from Kasparian, N., et al., (2009) Genetics in Medicine, 11(4): p. 265-278.
Timepoint [5] 333833 0
Q1 - Baseline
Secondary outcome [6] 333834 0
M7: Self-efficacy (confidence in receiving results despite ‘obstacles’ – will be measured with seven items adapted from Fisher, et al., (2012) Preventive Medicine, 55: p. 514-520.
Timepoint [6] 333834 0
Q1 - Baseline
Secondary outcome [7] 333835 0
M8: Uncertainty avoidance – will be assessed using Attitudes Towards Uncertainty scale
Timepoint [7] 333835 0
Q1 - Baseline
Secondary outcome [8] 333836 0
M10: Anxiety and Depression – will be assessed using the Hospital Anxiety and Depression Scale (HADS)
Timepoint [8] 333836 0
For participants who opt to receive their results, this will be measured at baseline (Q1), 2 weeks after receipt of results (Q2), and 12 months after receipt of results (Q3).

For participants who opt not to receive their results this will be measured at baseline (Q1), and 12 months after consenting to the study (Q3)
Secondary outcome [9] 333837 0
M11: Knowledge – 10 true-false questions have been developed to assess knowledge of polygenic risk and familial breast cancer.
Timepoint [9] 333837 0
For participants who opt to receive their results, this will be measured at baseline (Q1), 2 weeks after receipt of results (Q2), and 12 months after receipt of results (Q3).

For participants who opt not to receive their results this will be measured at baseline (Q1), and 12 months after consenting to the study (Q3)
Secondary outcome [10] 333838 0
M12: Stressful life events: will be assessed using the List of Threatening Experiences. Threatening life events may affect anxiety and distress levels and will be measured as potential confounding variable.
Timepoint [10] 333838 0
Q1 - Baseline
Secondary outcome [11] 333857 0
M13: Concordance with screening guidelines – will be assessed in accordance with the Australian national guidelines for mammography and clinical breast examination
Timepoint [11] 333857 0
This will be measured at baseline (Q1) and 12 month follow up (Q3) for all participants
Secondary outcome [12] 333858 0
M14: Intention to take up and actual uptake of preventative strategies – participants are asked whether they have undertaken risk reducing strategies including risk reducing surgery (surgery (bilateral mastectomy), and medication (i.e. tamoxifen and raloxifen). Responses include, "Yes", "No", and "No but I am planning to". For participants who indicate they plan to undertake a particular strategy, they are also ask asked indicate whether they plan to commence this strategy in the next 12 months.

Participants are also asked about lifestyle factors associated with breast cancer risk including, weigh and height (BMI), weekly alcohol consumption and weekly, and amount of moderate/intense exercise in a week.
Timepoint [12] 333858 0
For participants who opt to receive their results, this will be measured at baseline (Q1), 2 weeks after receipt of results (Q2), and 12 months after receipt of results (Q3).

For participants who opt not to receive their results this will be measured at baseline (Q1), and 12 months after consenting to the study (Q3)
Secondary outcome [13] 333861 0
M16: Regret over the decision – will be assessed using the Decision Regret Scale.
Timepoint [13] 333861 0
For participants who opt to receive their results, this will be measured 2 weeks after receipt of results (Q2), and 12 months after receipt of results (Q3).

For participants who opt not to receive their results this will be measured 12 months after consenting to the study (Q3)
Secondary outcome [14] 333862 0
M17: Test related distress, positive experience and uncertainty- will be assessed using The multidimensional impact of cancer risk assessment
Timepoint [14] 333862 0
For participants who opt to receive their results, this will be measured 2 weeks after receipt of results (Q2), and 12 months after receipt of results (Q3).

For participants who opt not to receive their results this will be measured 12 months after consenting to the study (Q3)
Secondary outcome [15] 333863 0
M18: Recall and interpretation of testing results – 3 items have been developed to assess recall and understanding of testing results.
Timepoint [15] 333863 0
For participants who opt to receive their results, this will be measured 2 weeks after receipt of results (Q2), and 12 months after receipt of results (Q3).
Secondary outcome [16] 333864 0
M19: Reasons for declining results – will be measured with 15 items adapted from Kasparian, N., et al., (2009) Genetics in Medicine, 11(4): p. 265-278.
Timepoint [16] 333864 0
For participants who opted not to receive their results this will be measured 12 months after consenting to the study (Q3)
Secondary outcome [17] 333874 0
M15. Satisfaction with Information Provided – participants will be asked to indicate how satisfied they were with the information provided by the genetic counsellor or geneticist at their results appointment on a 5 point Likert scale, with responses ranging from “very satisfied” (1) through to “very dissatisfied” (5). They will also be required to indicate whether the amount information received was “too much”, “about right” or “too little” and whether the language used was “too complicated”, “about right” or “too simple”.
Timepoint [17] 333874 0
For participants who opt to receive their results, this will be measured 2 weeks after receipt of results (Q2

Eligibility
Key inclusion criteria
Women enrolled in the ‘Variants in Practice’ study (ViP) provide a unique cohort in which to systematically ascertain the important psychosocial and clinical implications of genomic testing. The ViP study (HREC/11/PMCC/43) is enrolling a cohort of over 4,000 Victorian women and men who have a high-risk family history of breast cancer, that includes index cases with a personal history of breast cancer and their affected and unaffected relatives

Inclusion criteria: Women aged 18 years and over who are current participants of the ViP study. Additional criteria includes women where a known breast cancer predisposition gene has been excluded as the cause of their personal and/or familial breast cancer risk, and who are sufficiently proficient in English to provide informed consent and complete questionnaires.

Both index cases with a personal history of breast cancer, and their family members (affected and unaffected) will be invited to participate in this psychosocial study. This study will include women with a low (N=200) and high (N=200) polygenic risk score. Each group will then stratified by disease status, such that about 100 affected and 100 unaffected women are included in each study group.
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
- Women where a known breast cancer predisposition gene mutation (e.g. BRCA1/2) has been identified as the cause of their personal and/or familial breast cancer
- male participants of the ViP study. Men will be excluded as they constitute a very small proportion of ViP participants (<10%) and therefore as the small sample size will preclude a meaningful statistical comparison with the majority female cohort.
- Women who receive an intermediate polygenic risk score will also be ineligible, because intermediate results do not change a woman’s risk status and hence risk management advice in a clinically meaningful way.
- The funding parameters for this project means that it is not feasible to develop the study documentation and the assessment tools in multiple languages. Hence, women must be able to complete English language self-administered questionnaires to be eligible to participate in the study.
- Patients with obvious intellectual or mental impairment that may interfere with the patient's ability to understand the requirements of the study will also be excluded.

Study design
Purpose of the study
Educational / counselling / training
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety
Statistical methods / analysis
Sample size calculation: Based on similar previous studies (Kasparian et al, 2009), a sample size of 400 women is required to have 320 women completing the study with 215 receivers and 105 decliners (after adjusting for loss to follow up of approximately 20%). For a two sided test and based on a 5% significance level, this sample size will have 80% power to detect a clinically meaningful difference in the primary psychological outcome of breast cancer anxiety as measured by the Impact Event Scale (SD 14.2, range 0-75 scores) at the 2-week follow-up, between affected and unaffected women who receive a high PRS result (hypothesis 2c). A difference of seven scores (half a standard deviation) on the IES is considered a clinically meaningful difference to detect (Norman et al, 2003, Med Care).

Data analysis:
Data will be analysed using the SPSS program. Basic descriptive statistics, including means, medians, percentages, ranges and standard deviations will be calculated to describe the sample in terms of socio-demographic characteristics. The means of baseline key variables (M3 to M11) will be compared between receivers and decliners using independent samples t-test. Categorical data will be analysed by X2 test or Fisher’s exact test, as appropriate, whereas Student’s t-test for independent samples will be applied for continuous variables. Paired samples t–test will be applied to paired data of the baseline and follow up questionnaires. Equivalent non-parametric tests will used to analyse non-normally distributed data.

For each of the main outcome variables (M9 to M15), linear or logistic regression shall be used as appropriate. Further multivariate analyses will be used to adjust for potential confounding variables (e.g. age, parity, income). Appropriate regressions will be performed to investigate whether outcomes differ between receivers and decliners (hypothesis 1a) and between subgroups of affected and unaffected women (2c) and those receiving either a low or a high PRS (2a.ii). Repeated measurements will be analysed using linear mixed models to assess how outcomes change over time amongst receivers (hypothesis 2a.i and 2b). This approach adjusts for the repeated measures per person and also allows for missing values. Logistic mixed models will be used if there is a need to dichotomise an outcome variable. Correlations between women in the same family cluster will also be adjusted via mixed models.

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
Actual
3/08/2016
Date of last participant enrolment
Anticipated
1/06/2018
Actual
24/09/2018
Date of last data collection
Anticipated
1/11/2019
Actual
Sample size
Target
320
Accrual to date
Final
217
Recruitment in Australia
Recruitment state(s)
TAS,VIC
Recruitment hospital [1] 7848 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [2] 7849 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [3] 7850 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [4] 7851 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [5] 7852 0
Cabrini Hospital - Malvern - Malvern
Recruitment hospital [6] 7853 0
Royal Hobart Hospital - Hobart
Recruitment postcode(s) [1] 15791 0
3000 - Melbourne
Recruitment postcode(s) [2] 15792 0
3050 - Parkville
Recruitment postcode(s) [3] 15793 0
3084 - Heidelberg
Recruitment postcode(s) [4] 15794 0
3168 - Clayton
Recruitment postcode(s) [5] 15795 0
3144 - Malvern
Recruitment postcode(s) [6] 15796 0
7000 - Hobart

Funding & Sponsors
Funding source category [1] 296194 0
Charities/Societies/Foundations
Name [1] 296194 0
Cancer Council NSW
Country [1] 296194 0
Australia
Primary sponsor type
Individual
Name
Prof. Bettina Meiser, UNSW Sydney
Address
Psychosocial Research Group
Prince of Wales Clinical School
UNSW SYDNEY
NSW 2052 AUSTRALIA
Country
Australia
Secondary sponsor category [1] 295121 0
Individual
Name [1] 295121 0
Tatiane Yanes
Address [1] 295121 0
Psychosocial Research Group
Prince of Wales Clinical School
UNSW SYDNEY
NSW 2052 AUSTRALIA
Country [1] 295121 0
Australia
Other collaborator category [1] 279527 0
Individual
Name [1] 279527 0
A/Prof Paul James
Address [1] 279527 0
Familial Cancer Centre
Level 1, Peter MacCallum Cancer Centre
305 Grattan Street
Melbourne VIC 3000
Country [1] 279527 0
Australia
Other collaborator category [2] 279528 0
Individual
Name [2] 279528 0
Ms Mary-Anne Young
Address [2] 279528 0
Familial Cancer Centre
Level 1, Peter MacCallum Cancer Centre
305 Grattan Street
Melbourne VIC 3000
Country [2] 279528 0
Australia
Other collaborator category [3] 279529 0
Individual
Name [3] 279529 0
A/Prof. Kristine Barlow-Stewart
Address [3] 279529 0
Sydney Medical School - Northern
University of Sydney
Royal North Shore Hospital,
St. Leonards
NSW, 2065
Country [3] 279529 0
Australia
Other collaborator category [4] 279530 0
Individual
Name [4] 279530 0
Dr Tony Roscioli
Address [4] 279530 0
The Kinghorn Centre for Clinical Genomics
Garvan Institute of Medical Research
384 Victoria Street, Darlinghurst
NSW 2010
Country [4] 279530 0
Australia
Other collaborator category [5] 279531 0
Individual
Name [5] 279531 0
Prof Jane Halliday
Address [5] 279531 0
Public Health Genetics
Murdoch Children’s Research Institute
Fleming Road
Parkville
VIC, 3052
Country [5] 279531 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297435 0
Peter McCallum Cancer Center Human Research Ethics Committee
Ethics committee address [1] 297435 0
Ethics committee country [1] 297435 0
Australia
Date submitted for ethics approval [1] 297435 0
18/01/2016
Approval date [1] 297435 0
09/06/2016
Ethics approval number [1] 297435 0
HREC/16/PMCC/2
Ethics committee name [2] 297451 0
Tasmania Health and Medical HREC
Ethics committee address [2] 297451 0
Ethics committee country [2] 297451 0
Australia
Date submitted for ethics approval [2] 297451 0
01/03/2017
Approval date [2] 297451 0
06/04/2017
Ethics approval number [2] 297451 0
H0016395

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 1647 1647 0 0
/AnzctrAttachments/372743-Appendix A _Protocol V5_09.11.2016_clean.docx (Protocol)
Attachments [2] 1648 1648 0 0
/AnzctrAttachments/372743-16_10 Ethical Approval Certificate_9June2016.pdf (Ethics approval)
Attachments [3] 1649 1649 0 0
/AnzctrAttachments/372743-Appendix G_PICF V4_11.11.2016_clean.docx (Participant information/consent)
Attachments [4] 1650 1650 0 0
/AnzctrAttachments/372743-Appendix I_Educational Pamphlet V2_29.03.2016.pdf (Supplementary information)

Contacts
Principal investigator
Name 74030 0
Prof Bettina Meiser
Address 74030 0
Psychosocial Research Group,
Prince of Wales Clinical School,
Level 4 Lowy Cancer Research Centre
UNSW Sydney
NSW 2052
Country 74030 0
Australia
Phone 74030 0
+61 (2) 9385 0025
Fax 74030 0
Email 74030 0
b.meiser@unsw.edu.au
Contact person for public queries
Name 74031 0
Tatiane Yanes
Address 74031 0
Psychosocial Research Group,
Prince of Wales Clinical School,
Level 4 Lowy Cancer Research Centre
UNSW Sydney
NSW 2052
Country 74031 0
Australia
Phone 74031 0
+61 2 9385 0031
Fax 74031 0
Email 74031 0
t.yanes@student.unsw.edu.au
Contact person for scientific queries
Name 74032 0
Tatiane Yanes
Address 74032 0
Psychosocial Research Group,
Prince of Wales Clinical School,
Level 4 Lowy Cancer Research Centre
UNSW Sydney
NSW 2052
Country 74032 0
Australia
Phone 74032 0
+61 2 9385 0031
Fax 74032 0
Email 74032 0
t.yanes@student.unsw.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Due to the sensitive nature of participants data for this study, that includes personal genetic testing result, IPD will not be make available.


What supporting documents are/will be available?




Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbasePsychosocial and behavioral impact of breast cancer risk assessed by testing for common risk variants: Protocol of a prospective study.2017https://dx.doi.org/10.1186/s12885-017-3485-0
N.B. These documents automatically identified may not have been verified by the study sponsor.